Non-compliant balloon with compliant top-layer to protect coated stents during expansion

ABSTRACT

In order to minimize the potential for damage to bio-compatible and/or therapeutic-containing stent coatings, there is provided a compliant elastic sheath over layer between a non-compliant stent expansion balloon and an unexpanded stent, which is secured over the balloon with a securing crimp. This stent deployment assembly, which is mounted on a catheter, is maneuvered through a patient&#39;s body to a desired deployment site and then inflated to expand the stent to the desired diameter. During expansion, the compliant elastic material between the stent and the non-compliant balloon prevents non-compliant balloon-induced damage to the stent&#39;s coating, as well as preventing degradation of the non-compliant balloon by, for example, stent-caused punctures. The deflated non-compliant stent expansion balloon and compliant elastic sheath are then withdrawn from the patient&#39;s body, leaving the deployed stent at the desired implantation site with its coating substantially intact.

RELATED APPLICATION

This application is a Continuation of U.S. application Ser. No.10/035,158, filed on Jan. 4, 2002, incorporated herein in its entirety.

FIELD OF THE INVENTION

The present invention generally regards providing protection for acoated stent during its handling and use. More specifically, the presentinvention regards providing a compliant protective layer between a stentcoated with a polymer and/or a therapeutic substance, and anon-compliant inflatable balloon used to expand the stent into a desiredconfiguration in order to protect the stent coating from degradationduring deployment.

BACKGROUND

The positioning and deployment of medical implants is a commonoften-repeated procedure of modern medicine. Medical implants may beused for innumerable medical purposes, including the reinforcement ofrecently re-enlarged lumens, the replacement of ruptured vessels, andthe treatment of disease such as vascular disease by localpharmacotherapy, i.e., delivering therapeutic drug doses to targettissues while minimizing systemic side effects.

Such localized delivery of therapeutic agents has been proposed orachieved using medical devices such as catheters, needle devices andvarious coated implantable devices such as stents. These implants may bedelivered by securing them to the distal end of a delivery device,positioning the distal end of the device near a target delivery site,and then deploying the implant from the device to its desired position.The implant may be deployed by inflating the distal end of the device orthrough other forces that urge the implant from the device's distal end.When the implant has been coated this coating is susceptible to beingdamaged or completely removed from the implant during the deploymentprocess—an unwanted result.

The mechanical process of deploying the implant often exerts significantshearing and adhesion forces on and against the surface of the coatingof the implant. These forces can strip, damage or otherwise deplete theamount of coating on the implant. When the amount of coating is depletedthe implant's effectiveness may be compromised and additional risks maybe inured into the procedure. For example, when the coating of theimplant includes a therapeutic, if some of the coating were removedduring deployment, the therapeutic may no longer be able to beadministered to the target site in a uniform and homogenous manner.Thus, some areas of the target site may receive high quantities oftherapeutic while others may receive low quantities of therapeutic.Similarly, if the therapeutic is ripped from the implant it can reduceor slow down the blood flowing past it, thereby, increasing the threatof thrombosis or, if it becomes dislodged, the risk of embolisms.

The delivery of expandable stents is a specific example of a medicalprocedure that involves the deployment of coated implants. Expandablestents are tube-like medical devices, typically made from stainlesssteel, Tantalum, Platinum or Nitinol alloys, designed to support theinner walls of a lumen within the body of a patient. These stents aretypically positioned within a lumen of the body and, then expanded toprovide internal support for the lumen. They may be self-expanding or,alternatively, may require external forces to expand them, such as by aninflating a balloon within the stent's inner diameter. In either casethey are typically deployed through the use of a catheter of some kind.These catheters will typically carry the stent at their distal end.

Because of the direct contact of the stent with the inner walls of thelumen, stents have been coated with various compounds and therapeuticsto enhance their effectiveness. These coatings may, among other things,be designed to facilitate the acceptance of the stent into its appliedsurroundings. Such coatings may also be designed to facilitate thedelivery of a therapeutic to the target site for treating, preventing,or otherwise affecting the course of a disease or tissue or organdysfunction.

The term “therapeutic agent” as used herein includes one or more“therapeutic agents” or “drugs”. The terms “therapeutic agents” and“drugs” are used interchangeably herein and include pharmaceuticallyactive compounds, nucleic acids with and without carrier vectors such aslipids, compacting agents (such as histones), virus (such as adenovirus,andenoassociated virus, retrovirus, lentivirus and α-virus), polymers,hyaluronic acid, proteins, cells and the like, with or without targetingsequences.

Specific examples of therapeutic agents used in conjunction with thepresent invention include, for example, pharmaceutically activecompounds, proteins, cells, oligonucleotides, ribozymes, anti-senseoligonucleotides, DNA compacting agents, gene/vector systems (i.e., anyvehicle that allows for the uptake and expression of nucleic acids),nucleic acids (including, for example, recombinant nucleic acids; nakedDNA, cDNA, RNA; genomic DNA, cDNA or RNA in a non-infectious vector orin a viral vector and which further may have attached peptide targetingsequences; antisense nucleic acid (RNA or DNA); and DNA chimeras whichinclude gene sequences and encoding for ferry proteins such as membranetranslocating sequences (“MTS”) and herpes simplex virus-1 (“VP22”)),and viral, liposomes and cationic and anionic polymers and neutralpolymers that are selected from a number of types depending on thedesired application. Non-limiting examples of virus vectors or vectorsderived from viral sources include adenoviral vectors, herpes simplexvectors, papilloma vectors, adeno-associated vectors, retroviralvectors, and the like. Non-limiting examples of biologically activesolutes include anti-thrombogenic agents such as heparin, heparinderivatives, urokinase, and PPACK (dextrophenylalanine proline argininechloromethylketone); antioxidants such as probucol and retinoic acid;angiogenic and anti-angiogenic agents and factors; agents blockingsmooth muscle cell proliferation such as rapamycin, angiopeptin, andmonoclonal antibodies capable of blocking smooth muscle cellproliferation; anti-inflammatory agents such as dexamethasone,prednisolone, corticosterone, budesonide, estrogen, sulfasalazine,acetyl salicylic acid, and mesalamine; calcium entry blockers such asverapamil, diltiazem and nifedipine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, methotrexate, doxorubicin, daunorubicin, cyclosporine,cisplatin, vinblastine, vincristine, epothilones, endostatin,angiostatin and thymidine kinase inhibitors; antimicrobials such astriclosan, cephalosporins, aminoglycosides, and nitorfurantoin;anesthetic agents such as lidocaine, bupivacaine, and ropivacaine;nitric oxide (NO) donors such as lisidomine, molsidomine, L-arginine,NO-protein adducts, NO-carbohydrate adducts, polymeric or oligomeric NOadducts; anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, anRGD peptide-containing compound, heparin, antithrombin compounds,platelet receptor antagonists, anti-thrombin antibodies, anti-plateletreceptor antibodies, enoxaparin, hirudin, Warafin sodium, Dicumarol,aspirin, prostaglandin inhibitors, platelet inhibitors and tickantiplatelet factors; vascular cell growth promotors such as growthfactors, growth factor receptor antagonists, transcriptional activators,and translational promotors; vascular cell growth inhibitors such asgrowth factor inhibitors, growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; cholesterol-lowering agents; vasodilating agents; agentswhich interfere with endogeneus vascoactive mechanisms; survival geneswhich protect against cell death, such as anti-apoptotic Bcl-2 familyfactors and Akt kinase; and combinations thereof. Cells can be of humanorigin (autologous or allogenic) or from an animal source (xenogeneic),genetically engineered if desired to deliver proteins of interest at theinsertion site. Any modifications are routinely made by one skilled inthe art.

Polynucleotide sequences useful in practice of the invention include DNAor RNA sequences having a therapeutic effect after being taken up by acell. Examples of therapeutic polynucleotides include anti-sense DNA andRNA; DNA coding for an anti-sense RNA; or DNA coding for tRNA or rRNA toreplace defective or deficient endogenous molecules. The polynucleotidescan also code for therapeutic proteins or polypeptides. A polypeptide isunderstood to be any translation product of a polynucleotide regardlessof size, and whether glycosylated or not. Therapeutic proteins andpolypeptides include as a primary example, those proteins orpolypeptides that can compensate for defective or deficient species inan animal, or those that act through toxic effects to limit or removeharmful cells from the body. In addition, the polypeptides or proteinsthat can be injected, or whose DNA can be incorporated, include withoutlimitation, angiogenic factors and other molecules competent to induceangiogenesis, including acidic and basic fibroblast growth factors,vascular endothelial growth factor, hif-1, epidermal growth factor,transforming growth factor ∀ and ∃, platelet-derived endothelial growthfactor, platelet-derived growth factor, tumor necrosis factor ∀,hepatocyte growth factor and insulin like growth factor; growth factors;cell cycle inhibitors including CDK inhibitors; anti-restenosis agents,including p15, p16, p18, p19, p21, p27, p53, p57, Rb, nFkB and E2Fdecoys, thymidine kinase (“TK”) and combinations thereof and otheragents useful for interfering with cell proliferation, including agentsfor treating malignancies; and combinations thereof. Still other usefulfactors, which can be provided as polypeptides or as DNA encoding thesepolypeptides, include monocyte chemoattractant protein (“MCP-1”), andthe family of bone morphogenic proteins (“BMP's”). The known proteinsinclude BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7 (OP-1), BMP-8,BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, and BMP-16.Currently preferred BMP's are any of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6and BMP-7. These dimeric proteins can be provided as homodimers,heterodimers, or combinations thereof, alone or together with othermolecules. Alternatively or, in addition, molecules capable of inducingan upstream or downstream effect of a BMP can be provided. Suchmolecules include any of the “hedgehog” proteins, or the DNA's encodingthem.

When a polymer and/or therapeutic coating is haphazardly applied or hassomehow been removed during the stent's manufacture or delivery, thestent's effectiveness can be compromised. In certain circumstancesfaulty or ineffectively deployed stents can require the removal andreinsertion of the stent through a second medical procedure. Forexample, as the balloon at the distal end of the stent is inflated, toexpand and position the stent, frictional shear forces are createdbetween the surface of the catheter and the stent coating. Thesefrictional surface shear forces, as well as the adhesion forces betweenthe coating and the stent, act to tear away or unevenly redistribute thestent coating. Thus, the physical forces used to deliver the stent cancreate an abating result that reduces the overall effectiveness of adeployed coated stent.

During manufacture of assemblies of non-self-expanding stents andexpansion balloons over the distal end of a catheter, the stent may beplaced over the outer diameter of the unexpanded balloon and crimpedonto the balloon. Frequently, the stent expansion balloon is composed ofa non-compliant material, such as Polyimide, PET, HDPE or Pebax.Further, in order to minimize the profile of the stent assembly, it iscommon practice to form a number of wings in the wall of thenon-compliant balloon and fold the wings down along the side of theballoon prior to crimping the stent over the balloon. The folding ofwings in the non-compliant balloon minimizes the diameter of theuninflated balloon, and hence the diameter of the final crimped-on stentassembly. Moreover, when the stent expansion balloon is composed of anon-compliant material, the diameter of the expanded balloon, andtherefore also the expanded stent, is more or less independent of theballoon inner pressure.

There are some disadvantages associated with the use of non-compliantballoons in stent assemblies, both during manufacture of the assemblyand during inflation of the balloon and expansion of the stent. Forexample, during manufacture the hardness of the non-compliant balloonmay increase the difficulty in securing the stent over the balloon, suchthat often high crimping forces must be applied in order to adequatelysecure the stent to the non-compliant balloon. These high securementforces increase the risk for stent-caused punctures. Likewise, duringexpansion of the stent during implantation, the wings of thenon-compliant balloon move relative to the stent in a tangentialdirection. If the stent being implanted has a coating on its surface,the non-compliant balloon's sliding tangential motion may abrade orotherwise damage the stent coating.

Alternatively, a compliant balloon (i.e., a balloon composed ofwell-known elastic materials, such as Latex or silicone rubber) may beused for expanding a stent. Compliant balloons are softer thannon-compliant balloons, and thus permit the stent to obtain a better“grip” on the balloon, which in turn permits the stent to be more easilysecured to the stent using lower crimping forces. In addition, compliantballoons need not be formed and folded into a preferred pre-expansionshape like non-compliant balloons, as compliant balloons already have aminimal diameter in their unexpanded state. Compliant balloons alsoexpand principally in the radial direction, hence there is no tangentialsliding motion relative to the expanding stent, which in turn may reducethe chances of probability of stent coating damage during stentexpansion.

Compliant balloons have their own disadvantages, however. For example,the expanded diameter of a compliant balloon depends directly on theapplied pressure, requiring exacting control of inflation pressures toensure a stent is properly expanded. In addition, compliant balloonssometimes exhibit what is sometimes referred to as a “dog-bone effect”during expansion, wherein the portions of the balloon outside the lengthof the stent expand more that the portion of the balloon within thelength of the stent. Accordingly, use of compliant balloons to inflatenon-self-expanding stents may not be preferred in some applications.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus and method forovercoming the foregoing disadvantages. Specifically, there is provideda stent-expansion balloon made of a non-compliant material, over which acompliant elastic layer in the form of a sheath or tube or coating isplaced and an expandable stent is crimped thereover. The use of acompliant sheath permits the securing crimp to be made with lowercrimping forces, thereby decreasing the potential forstent-manufacture-induced damage to a coating on the stent.

The stent deployment assembly, which is mounted on the distal end of acatheter, is maneuvered through the body of a patient to a desiredimplantation location. The non-compliant stent expansion balloon is theninflated to expand the stent to the desired diameter. During expansion,the compliant elastic material between the stent and the non-compliantballoon prevents non-compliant balloon-induced damage to the stent'scoating, as well as degradation of the non-compliant balloon by, forexample, stent-caused punctures. The non-compliant stent expansionballoon is then deflated to disengage the non-compliant balloon and thecompliant elastic sheath from the stent. Once deflated, the catheterwith the deflated non-compliant balloon and the compliant elastic sheathmay be withdrawn from the patient's body, leaving the expanded stent atthe desired implantation site within the patient's body with asubstantially intact coating.

In one embodiment of the invention, manufacture of the stent deploymentassembly is conducted by placing a non-compliant balloon, in itsunexpanded condition, i.e., with folded wings, within a sheath made of acompliant elastic material that is held open by a purpose-builtexpansion fixture. Once the non-compliant balloon is placed inside thecompliant elastic sheath, the sheath is allowed to contract and conformto the outer surface of the unexpanded non-compliant balloon. Thisballoon sub-assembly is then placed within an unexpanded, coated stentof predetermined diameter, which is then secured to the balloonsubassembly by crimping the stent on top of the compliant elasticsheath. The use of a compliant elastic layer between the stiff metalstent and the non-compliant stent expansion balloon permits the stent tobe satisfactorily secured over the expansion balloon without use of highcrimping forces.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an oblique view of one embodiment of a stent assembly inaccordance with the present invention.

FIG. 2 is an oblique view of a non-compliant stent-expansion balloon inits uninflated state in accordance with an alternative embodiment of thepresent invention.

FIG. 3 is an exploded view of the stent assembly illustrated in FIG. 1,showing the components of the stent assembly.

FIG. 4 is a cross-section view of the stent assembly illustrated in FIG.1 along the longitudinal axis of the stent assembly, showing thearrangement of the stent assembly components

DETAILED DESCRIPTION

FIG. 1 illustrates an embodiment of the present invention, prior tostent expansion within the body of a patient. The stent deploymentassembly 1 shown in FIG. 1 may comprise: a non-self-expanding stent 2 ofwell-known material such as stainless steel, Tantalum, Platinum ofNitinol alloys and coated with at least one of a protective material, atherapeutic, or a therapeutic-bearing material; a compliant sheath 3 ofwell-known elastic material, such as Latex or silicone rubber; and anon-compliant stent expansion balloon 4 in a folded configuration withincompliant elastic sheath 3. Stent expansion balloon 4 may be made fromone of a number of well-known, relatively stiff polymeric materials,such as polyamide, thermoplastic polyamide, polyesters, polyphenylenesulfides, and polyethylene terephthalate (“PET”), and may be attached tothe distal end of a catheter 5 though its center in a conventionalmanner.

As shown in FIG. 2, in the present embodiment the non-compliant stentexpansion balloon 4 is prepared for use in the stent assembly by foldingthe uninflated balloon such that the balloon wall forms longitudinalwings 6 which wrap around the longitudinal axis of the non-compliantballoon. The folded stent expansion balloon 4 is thus formed into agenerally cylindrical shape. Another embodiment of folding thenon-compliant balloon into a cylindrical shape with minimal profile isto form so-called T-wings. These wings have the shape of a T incross-section and unfold without sliding tangentially underneath thestent. The crimp forces required, however, are still high.

The following describes the method of use of the above-described stentdeployment assembly. During a procedure for insertion and placement of astent in the body of a patient, stent deployment assembly 1, mounted onthe distal end of catheter 5, is maneuvered to the desired emplacementlocation by conventional means. At the desired stent emplacement site,non-compliant stent expansion balloon 4 is inflated via fluid pressuresupplied through catheter 5. As non-compliant balloon 4 begins toinflate, its folded wings 6 begin to unfold, expanding the balloon'sdiameter in the radial direction. This radial expansion is accompaniedby tangential movement of the outer edges of the balloon wings, whichslide across the inner surface of compliant elastic sheath 3. Becausecompliant elastic sheath 3 separates the edges of balloon wings 6 fromthe inner surface of stent 2, the protective or therapeutic coating onthe surfaces of stent 2 is not disturbed by the unfolding balloon wings,and any sharp edges on stent 2 are precluded from causing holes andleaks in non-compliant balloon 4. Once stent 2 had been fully expandedto the desired diameter, the pressure within non-compliant stentexpansion balloon 4 is decreased, allowing balloon 4 to contract, aidedby pressure applied by contracting compliant elastic sheath 3. Oncesheath 3 is contracted sufficiently to disengage from the inner surfaceof stent 2, the catheter to which non-compliant stent expansion balloon4 is mounted may be withdrawn from the patient's body without damagingthe coating on stent 2.

FIG. 3 is an exploded view of the principal components of the presentembodiment of the stent deployment assembly. The folded non-compliantballoon 4 is inserted into compliant elastic sheath 3 to form a balloonsubassembly. In order to facilitate the insertion of non-compliant stentexpansion balloon 4 into compliant elastic sheath 3, compliant elasticsheath 3 is expanded, for example by inflation within a purpose-builtfixture, or by mechanical means such as arms inserted into the sheathand moved radially outward. Following insertion of non-compliant stentexpansion balloon 4 into compliant elastic sheath 3, the sheath ispermitted to contract to conform to the outer surface of non-compliantstent expansion balloon 4.

After non-compliant stent expansion balloon 4 and compliant elasticsheath 3 are formed into a balloon subassembly, stent 2 is placed overthe subassembly and sufficient crimping forces are applied to securestent 2 over compliant elastic sheath 3 to preclude longitudinalmovement of stent 2 relative to compliant elastic sheath 3. The crimpingforces may be applied along the entire length of stent 2, oralternatively at distal end 7 or proximal end 8 of non-compliant balloon4, or at any combination of these locations. It is preferable thatcompliant elastic sheath 3 be relatively transparent to permit radioopaque markings on non-compliant balloon 4 (not shown) to be seen inorder to permit correct positioning of stent 2 prior to crimping overthe compliant elastic sheath 3. Due to the improved resistance to stentlongitudinal motion provided by the compliant elastic layer (as comparedto crimping the stent directly over the non-compliant balloon), theusual measures to minimize longitudinal motion such as hubs (polymerrings) or spiral inner sheaths can be left out of the stent assembly.Accordingly, because the usual measures are left out, the overallprofile (diameter) of the unexpanded stent assembly need not be anylarger than a usual non-compliant balloon-inflated stent deploymentassembly.

FIG. 4 provides a cross-section view of the foregoing embodiment. Inthis figure, non-compliant balloon 4 is shown after insertion intocompliant elastic sheath 3, and compliant elastic sheath 3 is shown witha closed end 9 over distal end 7 of balloon 4. Alternatively, compliantelastic sheath 3 may be an open-ended tube, or may be closed over theproximal only or closed over both ends of the non-compliant balloon.FIG. 4 further shows the position of stent 2 relative to the balloonsubassembly following crimping of stent 2 onto compliant elastic sheath3.

In order to ensure compliant elastic sheath 3 remains affixed tonon-compliant stent expansion balloon 4, a small amount of adhesive 10may be applied between the closed end of sheath 3 and balloon 4,preferably at a location outside the area upon which stent 2 is crimpedover the balloon subassembly. Alternatively, the adhesive may be placedbetween sheath 3 and balloon 4 at a location along the length of theballoon subassembly, as long as neither expansion of the balloon norelasticity of the sheath are compromised. As a further alternative,compliant elastic sheath 3 can be glued to the distal end of catheter 5and/or to a portion of catheter 5 adjacent to proximal end 8 ofnon-compliant balloon 4.

Further, as illustrated in FIG. 4, a lubricant 11 such as silicone maybe applied between compliant elastic sheath 3 and non-compliant stentexpansion balloon 4 along their lengths to permit the balloon's wings toslide more easily in a tangential direction when unfolding beneathsheath 3 during stent expansion. The lubricant improves the ease ofstent expansion while minimizing the potential for either tangentialmovement of compliant elastic sheath 3 relative to the expanding stent(caused by the expanding wings of non-compliant stent expansion balloon4) or damage to the compliant sheath caused by stent 2.

While the present invention has been described with reference to whatare presently considered to be preferred embodiments thereof, it is tobe understood that the present invention is not limited to the disclosedembodiments or constructions. On the contrary, the present invention isintended to cover various modifications and equivalent arrangements. Inaddition, while the various elements of the disclosed invention aredescribed and/or shown in various combinations and configurations, whichare exemplary, other combinations and configurations, including more,less or only a single embodiment, are also within the spirit and scopeof the present invention.

1. A method comprising the steps of: providing a medical implant sizedto fit within a body of a patient, the medical implant having a coatingat least on an interior accessible surface of the implant; providing acatheter having an inflatable balloon; providing an expandable sheath,the expandable sheath sized to fit over the inflatable balloon; coveringat least a portion of the inflatable balloon with the expandable sheath;placing the medical implant around at least a portion of the sheathafter the sheath covers at least a portion of the inflatable balloon. 2.The method of claim 1 wherein the sheath is transparent.
 3. The methodof claim 1 wherein the medical implant is a stent and wherein placingthe medical implant around at least a portion of the sheath after thesheath covers at least a portion of the inflatable balloon, includescrimping the stent around the sheath and the balloon.
 4. The method ofclaim 1 further comprising: inflating the balloon; deflating theballoon; and sliding the medical implant off of the sheath.
 5. Themethod of claim 1 further comprising: holding at least an end of thesheath open with an expansion fixture.
 6. The method of claim 4 whereinwhen the balloon is inflated the sheath applies pressure to the balloonto contract the balloon.
 7. The method of claim 1 further comprisingexpanding the sheath open with mechanical arms inserted into the sheath.8. The method of claim 7 wherein the arms are configured to moveradially outward.
 9. The method of claim 1 further comprising: placingan adhesive between the sheath and the balloon.
 10. The method of claim1 wherein the sheath is substantially transparent.
 11. The method ofclaim 1 further comprising: placing a lubricant between the elasticsheath and the balloon.
 12. A method for manufacturing an expandablestent deployment assembly, comprising the steps of: expanding in aradial direction a tubular sheath made of a compliant elastic material;inserting an unexpanded stent expansion balloon mounted on a catheterinto the expanded sheath stent assembly; permitting the expanded sheathto contract and conform to the outer surface of the non-compliant stentexpansion balloon; inserting the assembled non-compliant stent expansionballoon and compliant elastic sheath into an unexpanded stent; andcausing the stent to be in contact with the compliant elastic sheath.13. The method of claim 12, wherein the step of causing the stent to bein contact with the compliant elastic sheath further comprises crimpingthe stent over the compliant elastic sheath.